Search Results (44)

Environmental forces impacting public health include exposure to toxic substances, adverse childhood experiences (ACEs), diet, and exercise. Here, we examine the first two of these forces in some detail since they may be amenable to correction through cultural, medical, and practitioner intervention. At the same time, changing people’s dietary and exercise routines are likely more resistant to these interventions and are referred to only incidentally in this review. That is, societal efforts could prevent exposure to toxicants and ACEs—not necessarily requiring cooperation by the affected individuals—whereas changing diet and exercise practices requires an individual’s discipline. Toxic substances considered in this review include endocrine disruptors, arsenics, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the organic solvent, Trichloroethylene (TCE), and the Benzo[a]pyrene (B[a]P) produced from incomplete combustion of tobacco and other organic materials. Exposure to each of these toxic substances may have serious adverse health effects, especially in genetically more susceptible individuals. For example, children of mothers exposed to the endocrine disruptor, Atrazine, have significantly lower birth length, weight, and head circumference. Moreover, male offspring exhibit genital abnormalities, and all of these effects may be transgenerational. However, analyses of interactions among genes, the environment, and epigenetic modifications have already revealed distinctive individual risks of adverse reactions to toxic exposure. So, interventions through precision medicine might improve the health of those exposed individuals. Adults previously exposed to more than one ACE (e.g., child abuse and inter-parental violence) are more likely to develop anxiety, cancer, and diabetes. Detecting ACE exposures in children in the general population is fraught with difficulty. Thus, the risks of ACEs to our health remain even more insidious than exposures to toxicants. Nevertheless, higher provider compassion is associated with significantly better clinical outcomes for patients with these afflictions. For all these reasons, the first major aim of this review is to recount several of the major forces contributing to or impairing public health. Our second major aim is to examine mitigating influences on these forces, including social justice and provider compassion in the setting of precision medicine. Idealistically, these mitigators might eventually lead to the development of more cooperative and compassionate cultures and societies. Full article

Few investigations have been made to determine whether pharmaceutical drugs cause any generational effects. These effects can be divided into intergenerational and transgenerational effects. In insects, the F1 offspring of exposed individuals are considered to show intergenerational effects (as they have been exposed as germ cells or early embryos), while the F2 generation is fully non-exposed and considered to show transgenerational effects. Here, the common over-the-counter (OTC) drug, paracetamol, is investigated for genotype-specific responses and effects across generations on three life-history traits: fecundity, longevity, and spontaneous locomotor activity levels in the model species Drosophila melanogaster. Seven isofemale D. melanogaster lines were exposed to a high and intermediate dose of paracetamol determined by a dose–response curve. NMR investigations verified the long-term presence of paracetamol in the food substrate. Phenotypic effects of paracetamol ingestion were investigated on flies exposed to the drug and in their offspring and grand-offspring. The dose–response curve indicated genotype-specific responses to paracetamol. In the following experiment, all traits investigated displayed significant effects of paracetamol ingestion for at least one of the seven isofemale lines, and we detected strong genotype-specific responses to paracetamol. Fecundity tended to increase in individuals directly exposed to the drug whereas fecundity in the F2 generation was reduced (transgenerational). Longevity generally decreased in directly exposed individuals but tended to increase in F1 offspring (intergenerational). Paracetamol effects on spontaneous locomotor activity were primarily detected as transgenerational effects and were rarely seen in directly exposed individuals. However, across lines, no clear overall trend could be determined for any trait. The generational effects and marked genotype-specific response to paracetamol warrants further investigation of both genotype-specific responses and generational effects in general. Full article

COPD and asthma are lung diseases that cause considerable burden to more than 800 million people worldwide. As both lung diseases are so far incurable, it is mandatory to understand the mechanisms underlying disease development and progression for developing novel therapeutic approaches. Exposures to environmental cues such as cigarette smoke in earliest life are known to increase disease risks in the individual’s own future. To explore the pathomechanisms leading to later airway disease, mammalian models are instrumental. However, such in vivo experiments are time-consuming and burdensome for the animals, which applies in particular to transgenerational studies. Along this line, the fruit fly Drosophila melanogaster comes with several advantages for research in this field. The short lifespan facilitates transgenerational studies. A high number of evolutionary conserved signaling pathways, together with a large toolbox for tissue-specific gene modification, has the potential to identify novel target genes involved in disease development. A well-defined airway microbiome could help to untangle interactions between disease development and microbiome composition. In the following article, Drosophila melanogaster is therefore presented and discussed as an alternative in vivo model to investigate airway diseases that can complement and/or replace models in higher organisms. Full article

One method of crop protection is the application of a widely used group of pesticides—pyrethroids. As xenobiotics, sub-lethal doses of insecticides cause stress in pests, resulting in a change in the shape and size of their organs or bodies. The stress caused by pesticides may lead to acute destabilization of development, but also to transgenerational canalization through the process of genetic assimilation. Fluctuating asymmetry (FA), small random deviations between the right and left sides of bilaterally symmetrical traits, is an outcome of developmental instability and is a measurable indicator of phenotypic response to stress. We exposed four populations of the seed beetle Acanthoscelides obtectus to sub-lethal doses of cypermethrin for ten generations in a laboratory evolution experiment. Using geometric morphometrics, we analyzed size and shape changes and the level of fluctuating asymmetry in untreated beetles and in samples from the fifth and tenth generation. Exposure over ten generations led to an increase in the body size of the beetles, shortening of their pronotum and elongation of their thorax and abdomen. After ten generations of exposure to cypermethrin, FA levels decreased, indicating a canalization of development. This study provides new insights into the phenotypic markers of environmental pollution from agricultural activities. Full article

Grassland plants that endure livestock grazing exhibit a dwarf phenotype, which can be transmitted to clonal offspring. Yet to date, it remains poorly understood whether such transgenerational dwarf effects alter the plants’ response to shade. Here, we conducted a common garden experiment under sunlight and shade conditions with clonal Leymus chinensis offspring, the parents of which had endured livestock overgrazing (OG) and non-grazing (NG) in the field, respectively. Plant morphological, physiological, and transcriptomic analyses were carried out. The results indicated that NG offspring showed greater shade avoidance than OG offspring. That is, NG offspring exhibited greater plasticity of vegetative height and leaf width, which may be contributed to their greater photosynthetic capacity and gibberellin (GA3) content compared with OG offspring when treated with shade. In addition, RNA-Seq profiling showed that differentially expressed genes in NG offspring were mainly enriched in RNA modification and metabolic processes, which facilitated rapid response to shade. Phytochrome interacting factors (PIFs) promoted downstream shade marker genes in NG offspring by significantly downregulating the expression of PHYC, SPY, and DELLA. Our findings suggest that light conditions should be taken into account to better understand transgenerational dwarf effects induced by livestock grazing on grassland ecosystems. These results provide new insights into the inducible factors of phenotypic variations in grassland plants that experience grazing. Full article

Mealybug wilt of pineapple (MWP) is a destructive disease worldwide caused by a parasitic complex that includes Pineapple Mealybug Wilt-associated Viruses (PMWaVs) and mealybugs (Dysmicoccus brevipes), which concurrently act as vectors for these viruses. Reducing the mealybug population is key to managing MWP, which is achieved in intensive production systems through the use of insecticides. SA (salicylic acid), ASM (acibenzolar-S-methyl), BABA (β-aminobutyric acid), and MeSA (methyl salicylate) are key components of systemic acquired resistance (SAR), the defense mechanism of plants against biotrophic agents such as mealybugs. In this study, these compounds were applied either as pure chemicals and/or as a major constituent of plant extracts. Both the Hawaiian hybrid MD-2 and Queen Victoria tissue culture plants, as well as suckers used for vegetative propagation, were treated with these compounds by direct application on the soil of pineapple pots. Subsequently, five mealybugs were released on each plant or each daughter plant in case of a transgenerational experiment; then, after 45 days, the number of mealybugs was counted. Exogenous SA, ASM, and MeSA reduced the population of mealybugs by a minimum of 50% and up to 80%. These SAR-inducing treatments could be an interesting alternative for controlling mealybugs and are already used in other pathosystems. The SAR mechanisms behind this effect are yet to be confirmed by molecular and enzymatic markers. ASM and MeSA are promising treatments for pineapples using tissue culture plants or traditional shoots. Full article

Maternal obesity and/or high-fat diet (HF) consumption can disrupt appetite regulation in their offspring, contributing to transgenerational obesity and metabolic diseases. As fatty acids (FAs) play a role in appetite regulation, we investigated the maternal and fetal levels of FAs as potential contributors to programmed hyperphagia observed in the offspring of obese dams. Female mice were fed either a control diet (CT) or HF prior to mating, and fetal and maternal blood and tissues were collected at 19 days of gestation. Elevated levels of linoleic acid were observed in the serum of HF dams as well as in the serum of their fetuses. An increased concentration of eicosadienoic acid was also detected in the hypothalamus of female HF-O fetuses. HF-O male fetuses showed increased hypothalamic neuropeptide Y (Npy) gene expression, while HF-O female fetuses showed decreased hypothalamic pro-opiomelanocortin (POMC) protein content. Both male and female fetuses exhibited reduced hypothalamic neurogenin 3 (NGN-3) gene expression. In vitro experiments confirmed that LA contributed to the decreased gene expression of Pomc and Ngn-3 in neuronal cells. During lactation, HF female offspring consumed more milk and had a higher body weight compared to CT. In summary, this study demonstrated that exposure to HF prior to and during gestation alters the FA composition in maternal serum and fetal serum and hypothalamus, particularly increasing n-6, which may play a role in the switch from POMC to NPY neurons, leading to increased weight gain in the offspring during lactation. Full article

This article examines the experience and effects of a trauma-responsive program that uses creative methods to address the ongoing psychosocial impacts of transgenerational trauma and youth suicide, which disproportionately affect First Nations people in Australia. Our aim is to understand how the aesthetic (sensory-affective) dimensions of such a program serve to promote experiences of growth after trauma, manifesting in a sense of connection to both self and community. The paper focuses on the second of two immersive, experiential workshops delivered seven months apart in the regional town of Warwick in Queensland, Australia. In the light of self-reports of growth and personal transformation following the initial workshop, the paper examines the key drivers of such growth, focusing in particular on how trauma-related experience is metabolised through cultural containment. It builds on Bion’s concept of container/contained, combining analysis of the affordances of immersion. Framed in cultural rather than medical terms, the larger goal of the paper is to establish how cultural programs fill a gap in trauma informed support, facilitating the processing of trauma. Full article

Digital technologies are reshaping traditional static urban typologies, as the museum, urging a rethinking of how Cultural Heritage (CH) is experienced. The work presents the PALIMPSEST Project, an Interreg V-A Greece–Italy funded project, which proposes a dynamic, interactive, participatory, and personalized museum experience in the urban context of Ioannina, Greece, establishing an open-air, immaterial, immersive museum route in the city. The project’s innovative approach involved three methodological stages. In the first stage, a collection of past stories of the city was achieved through transgenerational collaboration of students and older generations. In the second stage, the collected material was organized to create an interactive mobile app, allowing users to access existing and add new stories, fostering bottom-up development. In the last stage, a museum experience was built around interactive installations from selected stories through co-creation processes and dispersed throughout the city’s public space, activated by the visitors via the app. PALIMPSEST established a hybrid, open-air museum route, connecting the ICH with the urban landscape, and creating personalized and unexpected experiences of the city. The project offers a novel way to reconceptualize the museum by integrating digital technologies, arts, storytelling, and active participation, bringing the museum into the open urban space. Full article

A novel protein, PID-5, has been shown to be a requirement for germline immortality and has recently been implicated in RNA-induced epigenetic silencing in the Caenorhabditis elegans embryo. Importantly, it has been shown to contain both an eTudor and aminopeptidase P-related domain. However, the silencing mechanism has not yet been fully characterised. In this study, bioinformatic tools were used to compare pre-existing aminopeptidase P molecular structures to the AlphaFold2-predicted aminopeptidase P-related domain of PID-5 (PID-5 APP-RD). Structural homology, metal composition, inhibitor-bonding interactions, and the potential for dimerisation were critically assessed through computational techniques, including structural superimposition and protein-ligand docking. Results from this research suggest that the metallopeptidase-like domain shares high structural homology with known aminopeptidase P enzymes and possesses the canonical ‘pita-bread fold’. However, the absence of conserved metal-coordinating residues indicates that only a single Zn²⁺ may be bound at the active site. The PID-5 APP-RD may form transient interactions with a known aminopeptidase P inhibitor and may therefore recognise substrates in a comparable way to the known structures. However, loss of key catalytic residues suggests the domain will be inactive. Further evidence suggests that heterodimerisation with C. elegans aminopeptidase P is feasible and therefore PID-5 is predicted to regulate proteolytic cleavage in the silencing pathway. PID-5 may interact with PID-2 to bring aminopeptidase P activity to the Z-granule, where it could influence WAGO-4 activity to ensure the balanced production of 22G-RNA signals for transgenerational silencing. Targeted experiments into APPs implicated in malaria and cancer are required in order to build upon the biological and therapeutic significance of this research. Full article

The effects of HS on the welfare of poultry have been reported to have a transgenerational effect on phenotype plasticity. The goal of our experiment was to determine whether parental exposure to HS would impair the performance, HPA axis response, or behavior of their offspring. We treated adult drakes and hens (n = 80 ducks/treatment) at peak lay with HS or the control temperature for 3 weeks and incubated eggs collected from the last 3 days of the experiment. We utilized 76 ducklings/parental treatment group: control (CON-F₁) and HS (HS-F₁). Weekly data for body weights, body condition scores (BCSs), and novel object test (NOT) were collected. At 3 weeks of age, the ducks (n = 6/treatment) were subjected to adrenocorticotropic hormone (ACTH/cosyntropin, 0.0625 mg/kg) challenge or vehicle as the control. Blood samples were collected at 0, 1, 2, 3, and 4 h relative to treatment for serum glucocorticoid and heterophil-to-lymphocyte ratio (HLR) analyses. All injected birds were euthanized with pentobarbital on the second day relative to ACTH administration, and the spleen and bursa were removed and weighed immediately. Duck level analyses were completed using one- or two-way ANOVA as appropriate. BCSs were analyzed using a chi-squared test. The HS-F₁ ducks had a lower hatch weight (p < 0.05) compared with the CON-F₁ ducks but no significant difference in growth rates during the 5-week period. NOT (n = 4) analyses showed that the HS-F₁ ducks had a greater fear response (p < 0.001) compared with the CON-F₁ ducks. Similarly, an ACTH stimulation test showed that the HS-F₁ ducks had significantly (p < 0.05) heightened corticosterone and HLR responses compared with the CON-F₁ ducks. The HS-F₁ ducks showed altered baseline and ACTH-stimulated levels of cortisol compared with the controls. Our data suggest that parental exposure to HS impacts the HPA response and fearfulness of the F₁ generation in Pekin ducks. Full article

Stress is associated with various epigenetic changes. Some stress-induced epigenetic changes are highly dynamic, whereas others are associated with lasting marks on the epigenome. In our study, a comprehensive narrative review of the literature was performed by investigating the epigenetic changes that occur with acute stress, chronic stress, early childhood stress, and traumatic stress exposures, along with examining those observed in post-mortem brains or blood samples of suicide completers and attempters. In addition, the transgenerational effects of these changes are reported. For all types of stress studies examined, the genes Nr3c1, OXTR, SLC6A4, and BDNF reproducibly showed epigenetic changes, with some modifications observed to be passed down to subsequent generations following stress exposures. The aforementioned genes are known to be involved in neuronal development and hormonal regulation and are all associated with susceptibility to mental health disorders including depression, anxiety, personality disorders, and PTSD (post-traumatic stress disorder). Further research is warranted in order to determine the scope of epigenetic actionable targets in individuals suffering from the long-lasting effects of stressful experiences. Full article

The aim of this manuscript is to understand the impact of childhood sexual abuse on the development of Post-Traumatic Stress Disorder (PTSD), Human Immunodeficiency Virus (HIV) exposure. and parental neglect in crack cocaine users, considering the role of gender. This study is a secondary database analysis of a sample from a multicenter cross-sectional study with 715 crack cocaine users receiving outpatient treatment in public mental health networks in six Brazilian capitals. Prevalence ratios were estimated by Poisson regression. In crack cocaine users with childhood sexual abuse, traumatic experiences seem to remain fixed through the development of Post Traumatic Stress Disorder (PTSD) in adulthood. Crack cocaine users with childhood abuse and PTSD in adulthood showed more sexual risk behaviors, including outcomes such as HIV (PR = 3.6 p < 0.001 for childhood abuse and PR = 3.7 p < 0.001 for PTSD). Furthermore, this traumatic trajectory affects the functional ability of crack cocaine users, especially women, to work thus impacting their inclusion and sense of social belonging. Such a chain seems to be reflected in the establishment of a circle of transgenerational transmission, to the extent that subjects with a history of abuse and PTSD reported more parental neglect towards their children. This study reinforces the importance of preventive public policies regarding early socio-emotional vulnerabilities and the need to support families, especially women, to avoid HIV and self-destructive outcomes such as crack cocaine use. Full article

Interactions between alien plants and local enemies in introduced ranges may determine plant invasion success. However, little is known about whether herbivory-induced responses are transmitted across vegetative generations of plants and whether epigenetic changes are involved during this process. In a greenhouse experiment, we examined the effects of herbivory by the generalist herbivore Spodoptera litura on the growth, physiology, biomass allocation and DNA methylation level of the invasive plant Alternanthera philoxeroides in the first- (G1), second- (G2) and third-generation (G3). We also tested the effects of root fragments with different branching orders (i.e., the primary- or secondary-root fragments of taproots) of G1 on offspring performance. Our results showed that G1 herbivory promoted the growth of the plants in G2 that sprouted from the secondary-root fragments of G1 but had a neutral or negative effect on the growth of the plants in G2 from the primary-root fragments. The growth of plants in G3 was significantly reduced by G3 herbivory but not affected by G1 herbivory. Plants in G1 exhibited a higher level of DNA methylation when they were damaged by herbivores than when they were not, while neither plants in G2 nor G3 showed herbivory-induced changes in DNA methylation. Overall, the herbivory-induced growth response within one vegetative generation may represent the rapid acclimatization of A. philoxeroides to the unpredictable generalist herbivores in the introduced ranges. Herbivory-induced trans-generational effects may be transient for clonal offspring of A. philoxeroides, which can be influenced by the branching order of taproots, but be less characterized by DNA methylation. Full article

In recent years, we have seen an increasing amount of evidence pointing to the existence of a non-genetic heredity of the effects of events such as separation from parents, threat to life, or other traumatising experiences such as famine. This heredity is often mediated by epigenetic regulations of gene expression and may be transferred even across several generations. In this review, we focus on studies which involve transgenerational epigenetic inheritance (TEI), with a short detour to intergenerational studies focused on the inheritance of trauma or stressful experiences. The reviewed studies show a plethora of universal changes which stress exposure initiates on multiple levels of organisation ranging from hormonal production and the hypothalamic-pituitary-adrenal (HPA) axis modulation all the way to cognition, behaviour, or propensity to certain psychiatric or metabolic disorders. This review will also provide an overview of relevant methodology and difficulties linked to implementation of epigenetic studies. A better understanding of these processes may help us elucidate the evolutionary pathways which are at work in the course of emergence of the diseases and disorders associated with exposure to trauma, either direct or in a previous generation. Full article